Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety

Abstract

Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb-drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.

Keywords: antioxidants; atherosclerosis; cardiovascular diseases; herbal medicine; hypertension; inflammation; medicinal plants; oxidative stress.

Figure 1

Pathological processes involved in the development and progression of CVDs. Several risk factors can predispose to CVDs. These can include hypertension, smoking, dyslipidemia stemming from an unhealthy diet, or endocrinopathies like diabetes mellitus, hypothyroidism, and aging. The risk factors can lead to pathological alterations most of which can be due to endothelial dysfunction or VSMC alterations. Endothelial dysfunction or VSMC alterations increase the risk of developing atherosclerosis and hypertension. Atherosclerosis and hypertension are themselves CVDs risk factors and enhancers for the development of other CVDs like myocardial infarction, coronary artery diseases, or stroke. VSMC, vascular smooth muscle cell; ECM, extracellular matrix; NO, nitric oxide; eNOS, endothelial nitric oxide synthase; iNOS, inducible nitric oxide synthase; Ox-LDL, oxidized low-density lipoprotein.

Figure 2

Ginseng. (A) Roots have the healing properties (from https://pngtree.com/freepng). (B) Chemical structure of Ginsenosides. (C) Ginsenosides protopanaxadiol (PPD) and Ginsenoside protopanaxatriol (PPT). R1 and R2 are side chains in different ginsenosides. Glc, glucose; Ara, arabinose; Rha, rhamnose.

Figure 3

Ginkgo biloba. (A) Leaves of Ginkgo biloba or Maiden Hair Tree (from https://pngtree.com/freepng). (B) Chemical structure of Ginkgolides. (C) Chemical structure of Bilobalides. (D) Structural skeleton of flavonoids. R1 and R2 are side chains.

Figure 4

Ganoderma lucidum. (A) Ganoderma lucidum (from https://pngtree.com/freepng). (B) Examples of the chemical structure of two Triterpenes from Ganoderma lucidum.

Figure 5

Gynostemma pentaphyllum. (A) Gynostemma pentaphyllum (Source https://pngtree.com/freepng). Examples of the chemical structure of Gynostemma pentaphyllum Gypenoside that are usually synthesized 20 S-Protopanaxadiol (PPD). (B) example of some chemical structures of Gypenosides.

Figure 6

Herbal therapies in the context of CVDs. Herbal preparations can exert protective effects by ameliorating the pathological effects exerted by CVDs risk factors. The herbal extracts can attenuate endothelial dysfunction and/or VSMC alterations by acting as, vasodilators, ROS scavengers, anti-oxidants, anti-inflammatory, anti-apoptotic, anti-hypertrophic, or anti-proliferative agents. This achieved through mechanisms that act in ECs only, VSMCs only, or through overlapping mechanism that act in both ECs and VSMCs. In ECs, herbal preparations can increase NO availability, decrease mitochondrial dysfunction and/or metabolic abnormalities as well as enhance angiogenesis. This can decrease the incidence of atherosclerosis and hypertension, which in return can decrease the risk of CVDs development. In VSMCs, the herbal extracts can modulate ECM deposition as well as cell migration, proliferation, and cell shape changes. VSMC, vascular smooth muscle cell; ECM, extracellular matrix; EC, endothelial cell; NO, nitric oxide; PPARY, peroxisome proliferator-activated receptor-gamma.